DESCRIPTION: The diversity created by the process of V(D)J recombination in B and T cells is fundamental to the development of an immune system that is able to respond to the myriad of potential antigens. However, since V(D)J recombination is an inherently dangerous genetic process that involves the formation of double-stranded DNA breaks, there is always the danger that improper repair or recombination will result in cancer. Therefore, recombination must be strictly controlled. However, the mechanisms governing V(D)J control are not well-defined. This proposal will use a gene-inducible whole organism system to determine how recombination is controlled in T cells. Studies such as these may ultimately provide strategies to prevent cancers arising from illegitimate recombination events.